Since 1999, scientists at AgResearch’s campus at Ruakura, Hamilton, have created genetically engineered cattle with the purpose of developing a herd of transgenic dairy cows. The aim of this particular research programme has been to engineer the genetic modification of cattle to produce milk-products that AgResearch repeatedly claims are able to improve human health and nutrition. After almost ten years of research, these claims remain totally unsubstantiated.

What is AgResearch?

AgResearch Limited is an independent, Crown-owned research and development company. The Minister of Finance and the Minister of Crown Research Institutes are its shareholders. It comprises three science groups, a commercial services group and has business units which deal with corporate governance and services.After-tax revenue for the year 2006-2007 for AgResearch and its subsidiaries was NZ$5.1 million.

Any enterprise that wants to experiment with genetic engineering technology or use genetically engineered organisms in New Zealand - in confinement, in field trials or in the environment - has to make an application to the Environmental Resource Management Authority (ERMA).

ERMA considers each application, the science submitted in support of it, and its implications for New Zealand.

To date, because ERMA has refused to take into account relevant scientific objections offered at every hearing, no formal application seeking ERMA Authority approval to use transgenic has ever been denied.

Submissions are invited on each application to ERMA. Anyone can monitor applications and make a submission in support or against any application.

Letter addressed to the Environmental Risk Management Authority, New Zealand.

Copied to the Prime Minister, the Right Hon. John Key, relevant Ministers, leaders of other political parties, and officials of Federated Farmers and Rural Women.

7 April 2010

Physicians and Scientists for Global Responsibility (PSGR) is a Charitable Trust. We have no political or commercial affiliations. Members are required to be qualified in a field of medicine, science and/or technology. The Trustees are listed at the end of this communication.

Our concerns about genetic engineering technology have been previously voiced in submissions and communications to the Environmental Risk Management Authority. To date, no advances have been made that persuade us to change our position, that uncertainty arising from the multiple levels of complexity in biological systems makes necessary a cautious and contained approach to risk. Despite apparently reassuring claims of greater control over what genetic elements are used, genetic engineering remains a hit and miss process with evidence of numerous failures and unexpected outcomes that have proven costly to agricultural and commercial interests. It is not a precise technology and holds no guarantees of safety for the environment. Moreover epigenetic effects and the indeterminate time-frames for effects arising from genetic expression make unexpected and ‘new’ hazardous outcomes particularly hard to predict.

We are writing to you now as we believe there is prima facie evidence that the presence of genetically engineered organisms in anything other than full containment and exclusion from the contiguous New Zealand environment (air, soil, water) represents an unmanageable and undefined scale of serious risk to our commercial export and tourism industries, and potentially the well-being of New Zealanders.

With the overturning of the High Court decision made by Justice Clifford (CA380/2009 [2010] NZCA 89), our concerns are again raised concerning the AgResearch Application (200223). The information given in the Application is non-specific and grossly inadequate, specifically in reference to:

Genetic engineering technology processes

· It does not detail which of many potential promoter sequences will be used;

· Which one of many potential terminator sequences will be used;

· Which of many potential marker genes will be used, and

· Whether the marker genes used will promote resistant to antibiotics in the experimental animals, nor which antibiotics will be used.

Introduced genes

· There is a total lack of information on or about which other specific genes will be used;

· The applicant has provided a list of organisms which would provide millions of different DNA sequences and/or genes for use. In many cases, the genomes of the organisms have not been fully mapped; thus the applicant is asking approval to place as yet undiscovered genetic sequences into multiple recipient animals, many of which are not native to New Zealand. Effectively, approval is sought for millions of distinct gene cassettes to be inserted into multiple species of animals, the consequences of which are unknown, and where there is potential for transgenes to escape into, and become entrenched in, the environment;

· Some of the listed organisms are known to cause serious illnesses or pathologies in animals and people;

· There is no description provided on how, or the order in which, DNA sequences and/or genes will be used or joined together, nor which specific vector system will be used in any particular case.

PSGR finds that the AgResearch Applications are seriously deficient in respect of the provision of information. The lack of information is so severe that it precludes any credible scientific risk management of the sort that ERMA has previously required. To the degree that ERMA has applied a science-based risk management methodology the application of established standards will be impossible. Without specific detail as to the genetic material being used no reasonable or valid assessment of safety can be undertaken.

PSGR finds that the breadth and vagueness of the information supplied by AgResearch raises serious doubts as to the integrity of the projects, and to the adequacy of ERMA’s processes in considering them, let alone extending existing approvals that are equally unsound. On the basis of the cavalier approach being taken by AgResearch, PSGR questions the ability of the organisation to take into account the known and unknown factors and the potentially serious consequences of its proposed work. We have lost trust in AgResearch to take a responsible attitude to risk, or to manage their projects responsibly, applying necessary caution.

PSGR wishes to be heard at the hearing. Please address details to Dr Elvira Dommisse at 48 Neville St, Christchurch 8024; (03) 942 2748; This email address is being protected from spambots. You need JavaScript enabled to view it. with a copy to PSGR, PO Box 8188, Tauranga 3145; (07) 576 5721; This email address is being protected from spambots. You need JavaScript enabled to view it..

1. General background

By way of introduction, PSGR would like to point out that Scotland has expressed strong opposition to genetically engineered (GE) crops being grown in its soil. The Scottish first minister, Alex Salmond, has stressed his unequivocal rejection of modified crops. His environment minister, Michael Russell, told the Independent newspaper, "We are not prepared to have trials of GE crops take place, and we are not interested in GE cultivation."

This opposition to GE technology also extends to Ireland. Earlier this month Northern Ireland signalled that it would join with the Irish Republic to keep the technology out of the entire island. Michelle Gildernew, the minister for agriculture and rural affairs, is quoted as saying: "Once we go down the GE route there is no going back. We need to keep Ireland GE-free."

It is interesting that the international Biotechnology Industry Organization has about 1,200 member companies. At the moment, only about a dozen of these organizations are developing GE animals.

It should also be noted that AgResearch’s GE animals are the only ones in Australasia. Why have Australians, generally more generous with their funding of scientific research than New Zealand, decided to steer clear of this type of research?

Even the US, which has been lax about regulating the cultivation of GE crops, has stipulated that full details be provided to the Food and Drug Administration (FDA) on the genetic engineering of animals for food, drugs or medical devices. The agency's regulatory control of animals will be considerably stronger than its oversight of GE plants and micro-organisms.

Guidelines tell companies what the FDA wants to know about their work at virtually every stage of creating a GE animal. For example, biotech firms will be asked to provide the molecular identity of the DNA inserted in an animal's genome, as well as where the DNA ends up and whether it descends unaltered through subsequent generations. The FDA also requires information on how the genetic alterations might change an animal's health, behaviour and nutritional value.

2. Failed or unproductive previous transgenic animal research in New Zealand

The failed Scottish company PPL conducted work on transgenic animals in New Zealand. They received permission from ERMA for the world's largest flock of GE sheep and then destroyed them all without autopsies. This work was unsuccessful and abandoned with no proper cleanup of the site.

The past performance of AgResearch on transgenic animals is little to be proud of. AgResearch has promised benefits for a decade from their GE cows. No results have been forthcoming. Jimmy Suttie has issued promises of unlikely cures for complex diseases.

”Dr Suttie said the transgenic cattle offered a cost-effective way of providing vaccines and medicines for human diseases, such as diabetes, growth-hormone deficiencies, cancer and hepatitis, and for rare diseases such as Pompe disease.” (Waikato Times, 25 October 2008).

He has also said he (and other scientists) will leave NZ if approval is not granted. This is not likely to concern most New Zealanders, as these skills are not widely regarded as vital to an environmentally sustainable long-term future in this country.

3. Animal Welfare

AgResearch’s application lists numerous animals to be host organisms for engineering. If approved, the institute will be allowed to develop unlimited numbers of assorted GE animals without the public knowing which genetic constructs they will use and how the animals will suffer increased rates of deformities and mortality.

AgResearch claims that there will be “no harm to animals”. However, it has completely overlooked the issue of animal welfare with respect to birth defects. Recent deformities recorded with their GE animals have included a female calf born alive on 23 December 2006 with a club foot and a fused neck, a male calf born alive the next day on 24 December 2006 with its rear fetlocks bent back, a male calf born alive on 17 August 2007 with the lack of a normal diaphragm and a male calf born dead on 19 September 2007 with un-inflated lungs. This information has come from the "Transgenic Animals" section of the Ruakura Animal Containment Facility’s annual report to ERMA.

Deformities sometimes occur naturally in farmed animals, but three serious deformities out of 36 live births within approximately one year are unusually high. Jimmy Suttie has said that ‘initial GE animal development is inefficient’. We assume that he is talking about the higher incidences of deaths and deformities. So far, photographs of such deformities have not been made available to the public. The Green party has asked Dr Suttie to confirm whether his experiments have also created calves with huge abdomens or with kidneys missing, or hearts fused to other organs.

Before approval of this work is even considered, detailed information, including photographs, needs to be released by AgResearch showing the abnormalities which result from the GE process. Based on results so far, the young of all animals involved are likely to suffer similar deformities to those AgResearch has already created in calves.

4. Animal models of human diseases

How can the scientists involved in these projects justify using a healthy large animal as a human disease model? The animals or animal cells are not human, so will most likely respond quite differently to humans or human cells. Simulating human diseases in animals also raises controversial animal welfare issues.

5. Horizontal Gene Transfer (HGT)

GE animal milk, waste and compost, faeces and placentas will all be deposited onto the soil. This opens up the route for horizontal gene transfer (HGT) of GE DNA into soil bacteria and other soil micro-organisms. AgResearch scientist Travis Glare has previously concluded that there is no evidence of HGT into soil bacteria in the sites where transgenic cattle have been found. The methodology by which these experimental results were obtained has recently come under scientific scrutiny. Papers based on past assumptions about HGT and on methodologies used to detect it have been discredited (Heinemann and Traavik, 2004; Lerat et al., 2005; Lerat et al., 2007; Babic et al., 2008). There is insufficient experimental detail given on the intended HGT work in this application. AgResearch need to say what their limits of HGT detection are and whether those limits are relevant to capturing gene transfers that can result in environmental damage.

A recently published study has examined soil invertebrates in a Roundup Ready corn for the presence and quantity of transgenic corn genes (cp4 epsps), with the goal of identifying the location of the transgenes in a soil food web.

The study tested macroarthropods, microarthropods, nematodes, and earthworms. It found evidence for large concentrations of transgenic DNA in animals from the food web associated with RoundUp Ready corn. This indicates that the transgene does not significantly degrade within the food web. Furthermore, the guts of these animals may provide opportunity for genetic transformation into native soil bacteria (Miranda, 2009).

It remains to be determined how far down the food web the transgene is detectable and whether or not the identified gene is available for transformation. It may be that animals associated with the soil food web provide an excellent starting spot for detecting genetic transformation in the natural environment.

Very little is known about the fate of transgenic animal and plant DNA in the soil ecosystem. Technical challenges of working in the soil environment, including high spatial variability and difficulties of extracting DNA without co-extraction of polymerase chain reaction (PCR) inhibitors (such as humic and fulvic acids), have been significant limitations to this area of research. However, recent advances in DNA extraction methodology and molecular techniques allow for the development of routine high-throughput techniques to examine comprehensively the fate of (plant) DNA in the soil environment (Gulden et al., 2005). Studies performed in controlled conditions have shown the possibility for the transfer of recombinant DNA from GE plants (and by extrapolation, GE animals) to competent bacteria (Gebhard and Smalla, 1998; Demanèche et al, 2001; de Vries et al, 2001). Although the transfer of transgenes from GM animals and crops to soil bacteria has not been reported in field soil, this is still regarded as probable, given demonstrations under controlled conditions. Horizontal transfer of transgenes in agricultural soil has not been extensively researched and more field studies are required (Heinemann and Traavik, 2004; Nielsen and Townsend, 2004).

6. Irrigating land with GE animal body fluids and effluent

The applicant says that milk will be fermented at pH 4, supposedly to destroy cells and then sprayed onto the land as irrigation. There is no guarantee that all cells will be lysed or that transgenic DNA will be destroyed. Hence biologically viable GE DNA may be directly sprayed onto the soil. Transfer of this DNA by HGT to soil bacteria could feasibly occur. The same goes for faeces and placentas deposited on the soil. There needs to be public notification of AgResearch’s intention to do this, particularly to neighbouring farmers, so that they have an opportunity to oppose such action.

7. New Zealand’s agriculture industry innovative and research-driven

In the application NZ’s agriculture is described as innovative and research-driven. This is not because of any GE work, as past GE work has not led to any successful innovations, but in spite of GE. As a country believed to be GE-free in its food production (excluding processed food), NZ can command premiums for its export crops and meat/dairy products. After the Sanlu melamine scare, NZ’s integrity as a high-quality dairy producer has taken a serious blow. Given that the Japanese and European markets are highly sceptical of GE foods, our overseas image is likely to suffer rather than improve, when word gets out about milk, meat and bio-pharmaceuticals from transgenic animals.

8. GE animals “could be more environmentally friendly”

AgResearch has previously mentioned that GE animals might be a more environmentally-friendly way to farm, with respect to reduced methane emissions. Why not investigate the breeds of dairy cow whose methane emissions are known to be considerably lower than the predominantly Jersey-Friesian mixed herds that are currently dominant in NZ? This could easily be learned from other countries who have already done this or who have always used these breeds.

The so-called “sustainability” argument can be and has already been addressed by organic, biodynamic and traditional non-(synthetic) chemical methods of farming. Such problems arise primarily from chemical farming methods rather than from a lack of genetic superiority of a breed of animal. Fertilizer run-off and leaching is the result of the use of highly soluble synthetic fertilizers. Organic methods build up the soil structure, fertility and water-holding capacity and therefore largely bypass these problems.

Organic or just thoughtful pasture management, i.e., mixed swards instead of ryegrass (Lolium perenne) monocultures, is also regarded as a positive step towards better stock health and possibly reduced methane and nitrous oxide production. Several species, e.g. timothy, cocksfoot, fescue and Phalaris provide more nutrition, are more drought resistant and are less prone to the Lolium endophyte problem that plagues perennial ryegrass. Most organic farmers include small quantities of a wide variety of grass species and herb species (e.g. chicory) in their pasture mix.

With such biodiversity in the sward, animals are able to select what they need for optimum nutrition. Some herbs are also deep-rooted and provide better soil structure. Trees and shrubs can be planted for shelter, forage and biodiversity. Application GMD08012 talks of the need to genetically engineer animals to improve parasite resistance (p.8). Many trees, including poplars and willows, contain phytochemicals , e.g., tannins, that also help protect stock from internal parasites and improve nutrition, with N.Z. flax also particularly beneficial (N.Z. Lifestyle Block, Oct/Nov 2008,pp21-23).

9. AgResearch’s 2020 Science Strategy

Should AgResearch take the time to become aware of all the innovative initiatives happening on existing organic farms and on farms generally using biological rather than chemical methods of farming, they would notice that considerable progress is being made on these outlined goals. This progress has been made without GE and that is what is attracting attention from our export markets.

There are at least two examples of such progress in NZ. The strategy says that “easy care” sheep are required. This no doubt means high health and self-shedding sheep. We already have them in NZ and they are called Wiltshires, originally from Britain. Wiltshires are large sheep that moult naturally each spring/summer. They have high fertility and twins are common. They have been bred for natural resistance to parasites and disease (www.organic-rams.co.nz). The ewes are good mothers and lambs have good growth rates. Lambs moult in their first summer, which bypasses any shearing labour costs for farmers. The low wool prices of today make this breed an excellent viable alternative sheep breed (www.wiltshire-sheep.co.nz). Dorpers are also healthy self-shedding sheep, but have not yet caught on in NZ (pers. comm., Graham Butcher, Rural Solutions, Gore).

The second example of high health, high fertility stock (sheep and cattle) being bred by conventional means are the Southland organic stock breeding farms Avalon Genetics (www.avalongenetics.co.nz) and Tim & Helen Gow (www.hardyhairyhorny.co.nz ). These businesses are very successful, because of the high quality of the breeds produced. Their meats are delivered to restaurants and buyers all over NZ.

Traits such as high health, high fertility and parasite resistance are complex and very unlikely to be produced using GE techniques. High birth mortality and birth defects recorded so far by AgResearch would confirm this.

10. Traits targeted by biotechnological research

Beneficial traits have not been shown to be assisted with GE. Reproductive efficiency has so far got worse in GE animals produced by AgResearch (see ERMA website). Marbling can already be successfully achieved by feeding stock with corn. Facial eczema resistance and parasite resistance have been effectively achieved using organic methods of control (see previous section). These always include the use of naturally-occurring plant or microbial treatments, nurturing of the soil to increase its fertility and water-holding capacity and a greater range of biodiversity of grazing and shelter species. Such biodiversity encourages the proliferation of beneficial macro- and micro-organisms.

Supplementation of animal feed with molasses, cider vinegar and other supplements go a long way towards maintaining healthy herds.

11. Changing milk and wool fibre characteristics

Milk composition varies considerably between different breeds of dairy cow. To engineer with the purpose of reducing allergens contradicts published research about GE organisms producing allergens as a result of major disruptions to the host’s DNA (Mayeno and Gleich, 1994; Inose and Kousaku, 1995; Ewen and Pusztai, 1999b; Prescott et al., 2005). The result could feasibly be the removal of one allergen, but the production of novel, unidentifiable allergens.

Wool fibre also varies considerably between various breeds of sheep and conventional crosses of e.g. a Romney crossed with a good wool-producing breed can achieve superior wool characteristics. Merinos already produce very durable wool of a superior quality. Wool has the advantage as a fibre of being durable, warm, non-flammable and ‘breathable’. Wool is also completely biodegradable if untreated with preservatives and flame retardants. No synthetic fibre can match this.

Incidentally, the Christchurch-based firm “Untouched World” has a thriving international business with its organic merino wool products.

12. “Unanticipated discoveries” and “very low or negligible risk”

The GE work of plants and animals carried out in NZ since the 1980s has never thrown up positive, commercially viable unanticipated discoveries. The only unanticipated discoveries so far have been poor-performing GE crop plants, GE-contaminated sites that should have been cleaned up and imported seed batches contaminated by GE DNA. This is hardly something to be proud of.

Procedures are said by the applicant to be of “a very low or negligible risk”. A low risk does not mean that effects of that event will be minimal or short-lived. This risk assessment is only based on available current research and subjective opinion. Future improvements with the detection of HGT for example, are likely to show that such events have always been occurring, but were not detectable.

13. Expression of GE genes in non-target tissue or body fluids

Aside from the higher risks of deformed animals, as has been acknowledged by AgResearch, there is also the risk that foreign proteins will be expressed in non-target tissues, e.g. blood or muscle tissue instead of or as well as milk. In addition to this, pharmaceutical proteins introduced into a cell could easily interfere with the basic cellular metabolism, so as to alter the overall composition of the cell.

Foreign proteins in GE animals may not be identical to the parent proteins. Any post-translational modification, however slight, could alter the potential toxicity or carcinogenicity of a protein (see section 17)

14. Segregation of GE material from the food chain

The application says that no products or waste from the transgenic animals will leave the containment facility. What about scavenging birds eating placentas or birds attacking the young animals? This is a definite possibility in a field situation and has not been considered by the applicant.

The transgenic DNA could survive a passage through the gut of such a bird. There is evidence that relatively long fragments of DNA survive for extended periods after ingestion. DNA may be detected in the faeces, the intestinal wall, peripheral white blood cells, liver, spleen and kidney, and the foreign DNA may be found integrated in the recipient genome. When pregnant animals are fed foreign DNA, fragments may be traced to small cells clusters in foetuses and newborns (Traavik and Heinemann 2007).

15. Creating a “sustainable, profitable pastoral farming industry”

This application bills genetic engineering as a way of improving herds to create a sustainable, profitable pastoral farming industry. ‘Biopharming’ has not and will not address challenges of the pastoral farming sector. Any farmer will tell you that the problems of this sector are related to soil fertility and soil moisture, reduction of methane emissions, reduction of pollution in waterways and high quality affordable feed when pasture growth is insufficient. AgResearch has previously argued that the “underlying costs of livestock production in countries such as those in South America are below that of N.Z.” The same could be said for China (Sanlu) and look where that has got Fonterra. We do not know exactly what occurs at all steps of farming and milk processing or whether farmers and dairy processing workers are being exploited or undercut. Food safety and questionable human rights or treatment of workers are always issues in developing countries. One only has to look at the clothing industry in China.

Furthermore, there will always be a demand by New Zealanders for locally-produced fresh milk, cheese, yoghurt and other dairy products. At a time when we should be reducing our carbon footprint, buying locally produced goods is imperative.

The application promotes this technology as being able to be used in NZ’s nutraceutical industry. However, a number of premium NZ brands of nutraceuticals, e.g., LifeStream and NFS have advertised themselves prominently as GE-free. This is a selling point for them locally and internationally. If nutraceuticals of GE origin were to go onto the market, presumably labelled as such, it is very likely that they would not sell well, given the current tide of opinion against GE foods and supplements. The GE tryptophan disaster, responsible for the deaths and permanent illnesses of hundreds of people, is still clear in the minds of many (Mayeno and Gleich, 1994). The applicant cannot therefore claim that this would create sustainable wealth for the NZ pastoral and biotechnology sectors.

The application (p.5, par.1) states that “(b)iotech animals can be the reactors that provide a more versatile and cost-effective means of producing therapeutic proteins compared to traditional cell culture systems”. This goes against the recommendations of the RCGM, which specified that animals should not be used as bioreactors.

The applicant also claims that livestock traits will be enhanced. What traits and how? No detail is forthcoming. Non-GE genetic enhancement of herds is already a thriving industry in NZ using conventional breeding, sometimes assisted by marker-assisted selection (MAS). Results of such breeding have been very forthcoming.

16. Safe alternatives to GE animals as biopharm factories

Cheap manufacturing has been cited as a reason for using animal as bioreactors to produce pharmaceuticals. However, these compounds may be produced using other non-biopharming technology. According to Elbehri (2005) there are 84 biopharmaceuticals on the market, while Goldstein & Thomas (2004) - see http://www.lincoln.ac.nz/story_images/3050_RR296_ s8982.pdf for further information and a full list of references - stated that during the last two decades, approximately 95 biopharmaceutical products have been approved by one or more regulatory agencies for the treatment of various human diseases including diabetes mellitus, growth disorders, neurological and genetic maladies, inflammatory conditions, and blood dyscrasias. All of these biologics, except perhaps one, are produced using non-biopharming methods. Instead, they are produced using cell culture, in which vats of mammalian or plant cells are grown in containment and are then processed to extract the target compound. The applicant argues that such “man-made” bioreactor vessels are inferior to “natural” GE animals producing transgenic proteins. However, the applicant has failed to provide evidence that the overproduction of human proteins in cells that never normally produce (sometimes synthetic) proteins is good for the health and well-being of the transgenic animals, or indeed of the human patients who will eventually consume these GE proteins.

The application assumes that transgenic animals have been validated as a suitable production platform for the production of human pharmaceuticals. Until complete results of comprehensive clinical trials have been published, this claim cannot be made. A protein may be changed by post-translational modification (e.g. altered glycosylation patterns) or may fold in a different way when it is made in an animal cell as opposed to a human cell.

The application says that transgenic animals are able to produce highly complex proteins that cannot be produced by other systems and closely resemble the protein produced naturally by the human body. It has been shown in transgenic plants that the introduction of the same gene into two different types of cells can produce two very distinct proteins. This was demonstrated in work on GE peas (Prescott et al., 2005). A bean amylase inhibitor, harmless when fed to mice in its natural state in beans, became harmful to mice when engineered into peas.

Mice that were fed with GM peas, modified with a gene from the closely related common bean (both in the Fabaceae family), were shown to have immunological damage, evident in their lungs (Prescott et al., 2005). The authors of the study said diversity in translational and post-translational modification pathways between species could potentially lead to discrete changes in the molecular architecture of the expressed protein and subsequent cellular function and antigenicity. They showed that transgenic expression of a plant protein (-amylase inhibitor-1) from the common bean (Phaseolus vulgaris L. cv. Tendergreen) in a non-native host i.e., the GM pea (Pisum sativum L.), led to the synthesis of a structurally modified form of this inhibitor. They also showed that the consumption of the modified inhibitor as compared with its native form, caused an antigen-specific (CD4+ Th2-type) inflammation in the lungs of mice.

The totally artificial nature of GE does not automatically make it dangerous. It is the imprecision in the manner by which genes are combined and the unpredictability in how the introduced gene will interact within its new environment which results in uncertainty. The balanced gene functions that have evolved together and which are preserved with traditional methods are lost with GE. Disturbed biochemical function may in turn lead to the production of novel toxins and allergens (Mayeno and Gleich, 1994; Inose and Kousaku, 1995; Ewen and Pusztai, 1999a,b)

18. Hazards of recombinant milk proteins

AgResearch and ERMA would be wise to learn from past mistakes overseas with recombinant proteins produced in milk. For years, the synthetic recombinant bovine growth hormone was (rBGH) injected into cows in the US to increase milk production (all information on rBGH milk reviewed in Epstein, 1996). It has caused much controversy and been the topic of much research since it was approved by the FDA in 1985. The FDA approved the commercial sale of unlabelled milk and meat from large-scale trials on cows treated with rBGH. FDA and industry claimed that rBGH had no adverse veterinary effects and that rBGH milk was indistinguishable from natural milk and safe for human consumption.

By 1990, evidence from published and unpublished industry sources had raised a wide range of concerns about the safety of rBGH milk. These included:

Contamination of rBGH milk with pus from mastitis and with antibiotics used in its treatment;

Contamination of milk with rBGH that FDA admitted differed significantly in its molecular structure from the naturally occurring growth hormone;

In spite of these unresolved veterinary and public health concerns, the FDA approved large-scale commercial use and sale of rBGH milk (November, 1993) and shortly after issued regulatory guidelines effectively banning the labelling of such milk.

Consumption of rBGH milk exposed infants and young children to IGF-1 levels well in excess of the safety margin (0.02mg/kg) identified in oral toxicity tests. Of further concern was the fact that pasteurization of rBGH milk increased IGF-1 levels by approximately 70%. In addition to this, IGF-1 in rBGH milk is more bioactive that IGF-1 in untreated milk. Several converging lines of research implicated IGF-1 in the initiation and promotion of breast cancer. This evidence raised serious concerns about the potential carcinogenic effects, particularly for female infants, of increased IGF-1 levels in rBGH milk and dairy products. Only recently has rBGH been driven off the market, largely as a result of the action of large milk processors refusing to use it. http://www.foodandwaterwatch.org/food/foodsafety/dairy/

AgResearch has said that “further approvals from other regulatory agencies such as NZFSA and Medsafe will be required...” NZFSA and FSANZ have a very poor record of “regulating” GE foods. They have in the past merely approved GE crops for inclusion in processed food without critical examination of commercial animals feeding tests.

Should the creators of GE animals apply to have GE cows, sheep or goats become part of the production chain for milk and meat, Food Standards Australia New Zealand (FSANZ) is likely to approve such applications without question. ERMA’s approval of this application will pave the way for such a move.

FSANZ has never rejected an application to import GE crops/foods into New Zealand. Since GE crops were first commercialised 12 years ago, FSANZ has approved over 50 varieties of GE food - ranging from corn and soy to potato and sugar beet. Many of these approved GE foods are not commercially available, yet it could appear that FSANZ are helping the makers of GE foods by paving the way for their smooth entry into our markets and supermarkets.

Recently, there have been many alarms raised internationally about GE foods that FSANZ has recklessly approved. In other countries, regulators have taken heed and reviewed the products in question. They have acted to ensure that GE foods which are considered to pose unacceptable risks are not approved. In some cases, these regulators have even banned the import of certain GE foods. Meanwhile FSANZ has either reached for the rubber stamp or turned a blind eye to imports of unapproved and untested GE foods. Further information on the controversial GE foods which FSANZ has approved of is listed in “Eating in the Dark”, a report commissioned by Greenpeace and reviewed by many scientists, including Professor Jack Heinemann (Gene ecologist and Director of the Centre for Integrated Research in Biosafety (INBI), School of Biological Sciences, University of Canterbury, NZ).

20. Human health problems and safety concerns with GE insulin

One compound that is routinely manufactured by GE, human insulin, has resulted in a raft of health problems that did not occur when the same patients were on naturally-occurring pig or cow insulin.

Dr Ernst von Kriegstein of the Paul-Gerhard-Trust in Wittenberg, Germany stated that there were problems during the initial studies of 'human' insulin in the USA because some patients had to discontinue the trials due to 'incompatibility'. Despite this, Novo Nordisk and Eli Lilly went ahead and doctors who converted patients on to human insulin were paid DM100 per patient. (http://www.iddtinternational.org/newsletters/newsletterapril2006.htm)

Complaints from hundreds of patients in Germany were ignored. They lost the early warning signals of an impending hypoglycaemic condition and some people had an allergic reaction showing up as anaphylactic shock and nausea. But human insulin was promoted as the wonder drug with the claim that incompatibility of human insulin was impossible, as its structure is identical with that found in the human body.

This theory is not supported by recent findings of the Institute for Quality and Efficacy in Healthcare (IQWiG) which relate to insulin analogues. Head of IQWiG, Prof. Peter Sawicki, stated: "Up to now we have only evaluated short-acting insulin analogues in patients with Type II diabetes. For these patients we can state, with certainty, that they bring no real advantages." Even the predicted ease of use was not confirmed. "It is a fairy story that insulin analogues offer an improvement to one's eating habits or lifestyle."

However, it is no fairy story that "experiments with animals and cell cultures suggest at least the patho-physiological possibility of carcinogenicity." In short: insulin analogues carry the risk of cancer. But this is not new; as early as 1992 all studies in patients of an analogue from Novo Nordisk were discontinued, as the result of the development of breast cancer in rats. Professor Chantelau warned: "Many cancers have a long period of latency. That for breast cancer can require 15 years. The industry has conducted many patient studies with human insulin and analogues - but no long-term studies into the possibility of cancer." That was also the warning from the IQWiG. Chantelau's main criticism of GE products is that "normally insulin is produced by specialised cells. It is a highly complex synthesis." The biotech production is not identical to that of nature: bacteria such as Escherichia coli or certain yeasts are genetically engineered so that they produce the molecules, or part molecules, of human insulin. Whether or not the folding of the amino acids is identical to that of human cells is not known - only the chemical formula is identical. How incompatibilities result for the patient has not been researched.

Referring to the refusal of many insurance companies to pay for imported pork insulin, Prof. Konrad Wink from the Pharmaceuticals Commission of the German Medical Association (AKdA) said "But that can be no reason to force a patient to switch to a product that may not be tolerated. It should never have come to this". The AKdA will recommend to the insurers that they should meet the costs of porcine insulin.

This report warns that Fonterra's future as a dairy-food exporter is in jeopardy because of AgResearch’s plans to manufacture pharmaceuticals and medical foods (p.7). It concludes that introducing a GMO into the NZ dairy sector has the potential to cause a minimum of NZ$539.6 million in losses to the dairy and tourism industries. Thus, such a biopharming endeavour would need to offset those losses before it could be viewed as a net positive for the NZ economy. The report warns that because of the importance to NZ’s economy of export-focused industries the reactions of overseas consumers are important. This is crucially important in the wake of the melamine-tainted milk products that were manufactured by Sanlu, of which Fonterra is a 43% shareholder.

22. Opposition to milk and meat from cloned animals

Application ERMA 200223 assumes that there will be a demand for compounds produced by GE animals. Opposition to animal meat or milk produced by genetic engineering and cloning is worldwide. European parliamentarians have recently voted with an overwhelming majority in favour of a proposal to ban cloning of animals for food. No fewer than 630 MEPs voted in favour and only 32 against. The motion urges the Commission to prohibit cloning of animals for food and any products from cloned animals and their offspring. Protagonists on both sides of the debate acknowledge that like GE animals,cloned animals are faced with a wide range of health problems, with a high death rate and a high incidence of disease.

The GE industry is built on the premise that genes and their functions can be isolated, patented, spliced into an organism, and controlled (Crick, 1957). There are now research-based reasons to believe that genetic engineering of both plants and animals is based on an outdated model of the workings of DNA, RNA and inheritance. A paper published in June 2007 by a consortium of scientists from 80 research organisations has provided evidence that genes do not necessarily behave in a linear fashion with information flowing one way, from DNA to RNA to protein, as was thought till now (The Encode Project Consortium, 2007). This central dogma that has been the bedrock of genetics and on which the genetic engineering industry is based, has been challenged by a growing collection of data, but scientists have been reluctant to revise the scientific principles established by the Watson-Crick discovery of the structure of DNA and the subsequent understanding of gene function (The Encode Project Consortium, 2007). This research raises serious questions about the established ways in which we assess the safety of GE organisms.

Now, unequivocal evidence comes from research organised by the US National Human Genome Research Institute, which has found that the human genome is not really a clear and organised set of genes but rather a tangle of overlapping, interacting genetic material that functions as a complex network, with highly nuanced gene regulation. Almost none of these mechanisms are understood. Not being able to predict how genes will behave strikes at the very basis of using genetic engineering as a tool to create new products. The biotechnology industry is built on the linear model of the “one gene, one protein” principle, postulated by scientists who created recombinant DNA in the 1970s. Now it is clear that some genes follow another paradigm: ‘one gene→one protein→multiple functions’ (Bhardwaj and Wilkinson, 2005).

Earlier, it was thought that genes had clearly defined functions. Therefore a gene from any organism could fit neatly and predictably into any other organism, however unrelated, and carry on its prescribed business. In this way, the Bt gene that produces a toxin in a soil bacterium is presumed to perform exactly the same function when inserted into cotton or rice plants.

The new research shows that this assumption cannot be upheld. The use of genetic engineering to create new products rests on the presumption that there is a universal, genetic code that sets the rules for creating proteins from DNA and that the rules are virtually identical across all organisms. Even before this research on the human genome, the theory of a uniform system for making new proteins was challenged by a number of scientific discoveries like the presence of large amounts of 'junk DNA' in all organisms and the fact that the highly complex human organism was found to have just 30,000 genes, a fairly small number considering the myriad functions a human being performs.

The new research casts the spotlight on the role of ‘junk DNA’, the large amounts of DNA detected during genome sequencing for which no clear functions can be ascribed. It is now accepted that the so-called “junk” DNA has a key regulatory role and it is of critical importance in regulating gene expression in organisms, a process about which there is as yet little understanding.

Apart from the new evidence and the presence of junk DNA, there are other findings that challenge the one gene - one protein foundation of agricultural biotechnology. One of these is the discovery that DNA is not the sole hereditary material and not the only means of transmitting information for new protein synthesis.

Understanding of the Mad Cow Disease and its link with the human Jakob-Creutzfeldt disease shows that both diseases can be passed from generation to generation not via genes, but via a protein molecule called a prion. Pioneering work done in the US by Stanley Prusiner, Susan Lindquist and Eric Kandel indicates that prions mediate a form of protein-based information flow, which seems to be important in a variety of biological processes. If we then add what is being discovered about the other ways in which RNA acts and the process of RNA interference, the reliability of genetic engineering becomes questionable.

RNA’s normal role is to carry a message from the DNA to the cytoplasm where it provides the direction for making proteins. Now it appears that ordinary RNA can enter a cell, seek out a gene’s protein-making template and then destroy it. This process is called RNA interference.

A complex, interactive network of genetic material incorporating so-called ‘junk DNA’, prions as units of heredity and the phenomenon of RNA interference, invalidates the premise on which biotechnology has been founded. Evidence that gene expression is complex and non-linear begins to explain why so many things go wrong during the process of genetic engineering and why predicting its outcome remains a gamble. This opens up the question about the extent to which genetic engineering can be considered accurate and predictable as a ‘manufacturing process’.

24. Risks of “wide” crosses of species boundaries performed in a highly artificial manner

The risks of animal/human transgenics have been in the news in the UK recently, with Lord Winston planning to transplant organs from GE pigs into human recipients. He is to begin breeding GE pigs in the next three months to produce hearts, livers and kidneys for transplanting to humans. Winston has pioneered a technique to create pigs with “humanised” organs that he claims will not be rejected by the patients’ immune systems.

Xenotransplantation is being fiercely opposed by ethicists. In a report for the Department of Health in 2003, Professor Sheila McLean, director of the Institute of Law and Ethics in Medicine at Glasgow University, warned the government that potentially lethal viruses could be passed from pigs to humans. http://www.timesonline.co.uk/tol/life_and_style/health/article4692850.ece

25. Criticism of GE hype coming from within the industry

In a very recent editorial, Nature Biotechnology 26, 837 (August 2008) has this to say:

Many DNA constructs used in both plant and animal GE work involves the use of antibiotic resistance genes. Most of the time, these genes end up in the final product, be it swine or soy. As anyone who has taken an introductory biology course could tell you, many bacteria will incorporate DNA from their environment and useful genes will even be transmitted between species. Thus, by releasing these biotech "products" into the environment, we are hastening the end of the golden age of antibiotics.

As if that isn't bad enough, consider the virology issues involved with interspecies tissue transplants. A virus well-adapted to swine would be non-lethal to swine. In fact, it may cause no clinical manifestation whatsoever. That same virus, when introduced into a human, may prove to be quite lethal. Consider that the current model used to explain the emergence of HIV postulates that it was initially transmitted to humans from bushmeat (primates), probably by direct blood to blood contact. So, these transplant-ready swine can be HIV- and hepatitis-free, but what surprises do they hold? I seriously doubt that clinical and outdoor trials will be large or comprehensive enough to assure our safety.

There are hundreds of thousands of acres of genetically modified (GM) crops being grown around the world, but they are not at present addressing key agricultural problems for poor farmers, such as salinity, desertification and drought. Nor are they addressing problems such as malnutrition. Many nations in Africa have a ban on GM seeds.

Although biotech has addressed a few orphan diseases, produced new therapies in infectious disease, cancer and autoimmune disorders, and recombinant versions of biologics for diabetes and growth disorders, it hasn't delivered on the promised 'cures' of genetic therapies or even the wide adoption of molecularly targeted medicine. Certainly, it hasn't done much to address disease and malnutrition among the world's poor.

In biotech, the new 'thing'-whatever it has been at the time (interferons, antisense, sepsis therapies, antibodies, genomics, functional genomics, structural genomics, proteomics, RNA interference)-is constantly put forward as the 'solution' (usually with a concurrent stampede of start-up activity and investment). Genomics and other 'omics’ were vaunted as solutions to the need for personalized medicine, a need that was poorly defined. Protein drugs were offered as wonder molecules, targeting diseases specifically and finally.

It is time for biotech communication to be done right. And it is time that the industry and its lobby organizations learnt that pushing one-dimensional hype about biotech solutions is counterproductive.

Conclusions

Recent research (2007) has demonstrated that the science behind such transgenic animal ventures to be flawed as the one protein – one gene hypothesis is no longer regarded as valid. Large amounts of transgenic protein/s in an animal cell are very likely to disrupt the composition of the animal cell. The human or synthetic proteins may be altered by translational modification or differential folding in such a way that they no longer have identical properties to their natural counterparts. GE insulin and recombinant bovine growth hormone are examples of GE proteins not behaving as predicted. They are also an example of the lack of regulation by the US FDA and a lack of a pre-cautionary approach.

Animal welfare has not been and cannot be dealt with as long as transgenesis and cloning of animals occurs. Past records of similar ventures should serve as a warning of what can go wrong.

HGT has been shown to occur in experimental situations and claims that it “cannot be detected (therefore does not occur)” in the field have been dealt with by research that demonstrates inhibition of the PCR technique and difficulties with the sensitivity of such assays. A new study (Miranda, 2009) has found evidence for large concentrations of transgenic DNA in animals from the food web associated with RoundUp Ready corn. This indicates that the transgene does not significantly degrade within the food web. Further, the guts of these animals may provide opportunity for genetic transformation into native soil bacteria.

Past ventures in New Zealand involving transgenic animals and the cloning of animals have been failures. A decade of such “research” has thrown up nothing beneficial for New Zealand. Given that this work is so expensive, research money would be much better spent on truly sustainable biological non-GE ventures like organic agriculture and pasture management, different breeds of animals and aiming to produce animal products for which there is an established and expanding market. Organics has already achieved this and there is a continuing rise in demand for such products, both in NZ and overseas.

There are currently established non-GE methods for producing bio-pharmaceuticals that do not involve animals as “bio-reactors”. This method (cell culture in vats) bypasses cruelty to animals and bio-safety risks for human patients on GE drugs.

Signed by Trustees and Members of Physicians and Scientists for Global Responsibility

From the July/August issue Organic New Zealand (www.organicnz.org)

Q: When is a field containment facility for holding GM-livestock no longer capable of effective containment?

A: After you’ve made many big holes in it!

That’s at least one answer … but you will be very unlikely to find any holes in the Ruakura security fence! The highly touted double-perimeter electrified fence of Ruakura’s GM-livestock field containment facility has by all reported accounts remained intact while holding their GM-cattle.

However, the same cannot be claimed with any measure of confidence when it comes to containment of the transgenes and gene products themselves. Understandably, the transgenic-DNA, purposefully engineered as a cellular genetic component of the GM-cattle, remains in existence even after each animal’s death. In this case, the double-perimeter fence has been an irrelevant security structure from the outset, as it is clearly unable to prevent the physical movement of transgenic-DNA through the natural boundaries of the field containment facility (FCF) into the surrounding unregulated soil environment

The answer to the above conundrum is a direct reference to the increasing number of two-metre deep pits that have been deliberately and repeatedly excavated over the past ten years inside the containment facility. Curiously, and in both ERMA-speak and AgResearch-speak, these holes are still euphemistically referred to as ‘offal holes’.

‘Offal holes’ is an absurdly misleading term for these soil structures that are deep, unlined, open-air pits, constructed to have sufficient working capacity to periodically receive and accommodate whole carcasses (up to perhaps a tonne at a time!) from expected GM-cattle mortality. As open field installations, these ‘offal holes’ or burial pits, whether active (a few) or abandoned (quite a lot), are naturally exposed to all seasonal extremes of climate, particularly rainfall, throughout each and every season. Some of the ‘offal holes’, with their slowly liquefying and decomposing contents, have experienced almost ten complete seasons of ‘in-soil residence’.

Irrespective of whether ERMA initially classified AgResearch’s applications as either F for field trial (i.e. GMF 98009) or D for development (i.e. GMD02028), field management of these projects has specifically required the GM-cattle to be confined in Ruakura’s field containment facility. This field facility is now reported to be holding 96 GM-cattle, mostly GM-dairy cows, being the livestock products of Ruakura’s on-going attempts to develop a transgenic dairy herd.

So, as termination of the above transgenic-cattle projects draws closer, what are we to now make of AgResearch’s quite recent presentation in February 20081 that it is preparing to launch a suite of applications covering four new GM-animal development programmes?

As announced, AgResearch expressed its intentions for two of these new GM-animal programmes to be conducted under field containment conditions. While both AgResearch and ERMA, to date, have been reluctant to release more details of any formal applications, it is clearly obvious that these recent AgResearch initiatives strongly suggest construction of at least one and possibly more additional field containment facilities at unspecified locations in New Zealand. Their research projections do not preclude consideration of transporting GM-animals between such field facilities.

A simple on-line re-examination of ERMA Decisions2 of AgResearch’s original applications GMF 98009 (Parts 1 and 2) and GMD 02028, together with AgResearch’s mandatory annual reports to ERMA3 can provide even the casual inquirer with sufficient clues to conclude that up to this point in time ERMA has chosen to be selective in applying its key statutory responsibility under the HSNO Act solely in terms of containment, while AgResearch has clearly continued to perceive its GM-research ventures of primarily engineering GM-animals as development of transgenic biological factories. But to date neither body, either jointly or separately, has displayed any convincingly serious scientific direction of research, or acknowledged any responsibility, to develop scientific strategies for evaluation of the actual environmental risks and safety of the existing GM-hotspots known as ‘offal holes’ ... each one now likely to contain many tonnes of GM-animal tissues at varying stages of in-soil liquefaction and decomposition.

Importantly, it is the inevitable consequence of there being both abandoned and active unlined soil-burial pits, plentifully stocked with decomposing GM-animal parts in direct and continuing contact with the soil environment that surely further erodes any credibility that the existing Ruakura field facility now has any significant capacity (if it ever did) of retaining the transgenes or their genetic products. As a unit, the field containment facility may well be at, or even beyond, its ‘best by date’. Site management may genuinely be wondering where to excavate the next ‘offal hole’. Even if total and immediate closure of the Ruakura field containment facility in its current state were to be implemented, major unknowns about the natural physical and biological events that govern the fate of animal-transgenes deliberately buried under such conditions are likely to remain unanswered far into the future. This may be what the ‘business as usual’ ethos might willingly wish to dictate, but that is simply not good enough!

So … why would anyone formally approve construction of any GM-animal containment field facility elsewhere in New Zealand, with ERMA issuing instructions to its field managers to run it in a similar manner to the present Ruakura facility?

As for Ruakura’s present GM-animal field containment facility, it now poses a significant environmental threat in terms of GM-offal holes. Justifiably, it should be closed and the site officially and indefinitely excluded from livestock farming of any kind into the foreseeable future.

Dr A Neil Macgregor, 11 April 2008. Full bio http://www.psgr.org.nz/index.php/biographies/18-trustees/27-a-neil-macgregor

** Check out GE Animal Watch on http://www.psgr.org.nz for updates and developments.

**Anyone can make a submission when AgResearch makes an application to ERMA. Monitor Applications open for submission on < http://www.ermanz.govt.nz/consultations/consult-apps.html >See how to make a submission on < http://www.ermanz.govt.nz/consultations/howsubmission.html >.